This invention is directed to a process for the prevention of dental caries and periodontal disease in animals which comprises contacting the dental surfaces with an effective amount of a thiouronium phosphonate chemotherapeutic agent. Advantageously, an appropriate pharmaceutically acceptable carrier such as a toothpaste, tooth powder or mouthwash can be used as the phosphonate vehicle.
Dental disease in animals is one of the most pervasive, non-life threatening medical problems encountered by man, affecting nearly all individuals at some time during their lives. The two most common dental pathologies are dental caries and periodontal disease. There are differing opinions as to the etiology of these diseases, but in all theories there is one common denominator--the presence of an acid-producing, acid-tolerating microorganism.
The dental decay process starts with the demineralization of the tooth enamel. The utilization of dietary carbohydrates by the bacteria in the synthesis of ATP produces an acidic metabolic waste product which, when contacted with dental enamel, initiates decay. This is followed by a progressive loss of tooth enamel.
Presumably, the normal dynamics of the oral cavity such as chewing, swallowing, the movement of the tongue or the flow of saliva would inhibit the accumulation of acid on the dental surfaces. However, because of the synthesis of dental plaque, the bacteria and their acidic waste products are held in contact with the tooth surfaces for a time sufficient to begin the demineralization process of the enamel.
Plaque is thought to be a soft, organic matrix consisting of a mixture of salivary glyco-protein and bacterial extracellular polysaccharides. It is within this sticky mass that bacteria become embedded. The matrix rapidly thickens on the surfaces of the teeth after eating and becomes an adhesive film which cannot be removed by the dynamics of the oral cavity or be washed off with water. Plaque, then, plays a significant role in the etiology of dental caries as it effectively serves to bind the bacteria to the dental surfaces and buffers the effects of saliva and other self-cleaning mechanisms of the mouth.
Several genera of oral bacteria have been isolated and are known to be cariogenic. The filamentous organisms of the Actinomyces genus, Nocardia, various strains of lactobacilli, and the streptococci have all been implicated in the decay process. Of the genera mentioned, the largest group involved in dental decay are the streptococci. Representative organisms which inhabit the oral cavity include S. mitis, S. mutans, S. salivarius, and S. sangius. The most important of these in terms of odontopathic effect is S. mutans. The ability of S. mutans to produce dental disease in man is well documented. It has been found that animals which tend to have a higher incidence of dental caries also have a greater concentration of S. mutans in the oral cavity.
The greater cariogenicity of S. mutans seems to be related to two factors which are of critical importance in the decay process. First, S. mutans has been termed a primary plaque former. The organism has the capability of producing greater quantities of extracellular polysaccharides, one of the components of the plaque matrix. Secondly, S. mutans has the capacity to produce greater quantities of acid than other streptococci which inhabit the oral cavity. These two metabolic processes are carried on simultaneously and the effects are significant. For example, when sucrose is metabolized by S. mutans, it is broken down into its component sugars, glucose and fructose. The glucose forms the dextran chain of the polysaccharide portion of plaque, while the fructose is further metabolized to lactic acid which is then held in close proximity to the dental surface to initiate or propagate the decay process.
Plaque has also been shown to be important in the etiology of the periodontal disease process. Periodontal disease affects the tissues surrounding and supporting the teeth, such as the periodontal membrane, the cementum, the alveolar bone and the gingiva. As these tissues weaken, the teeth gradually loosen and ultimately become unable to function in mastication.
The role of plaque in the periodontal disease process is similar to that in dental caries. It provides an adhesive covering over the periodontium whereby the bacteria are brought into contact with the soft connective tissue. It also acts as a buffer to the normal self-cleaning mechanisms of the oral cavity and provides an anaerobic environment which is essential to the survival of the microorganisms.
Generally, bacteria cited as being cariogenic have also been implicated in the periodontal disease process. Most notably is the deleterious effect of S. mutans on alveolar bone. Sharawy and Socransky discovered a significantly greater alveolar bone loss in laboratory mice and rats exposed to S. mutans as compared to non-exposed control groups (46 Journal of Dental Research, 1385, 1967). Other bacteria known to be involved in the periodontal disease process include Streptococcus salivarius, Actinomyces naeslundii, and various strains of Rothia, Neisseria, and Bacterionema.
Historically, the control of the dental disease process has focused on three separate areas: diet modification, host resistance, and bacteria-directed control. The diet modification approach has met with little success. It comprises eliminating from food sweeteners such as sucrose or the substitution of a non-hydrolyzable sugar such as xylitol. The elimination of sucrose from the diet involves changing eating and cooking habits which most people are not ready to make. The use of xylitol is feasible, but may be prohibitively expensive.
Attempts directed at increased host resistance to dental disease have received the most attention over the years. Procedures such as enzyme inhibition of plaque formation, resin-based plastic sealants over the articulating surfaces of the molars, and vaccine immunizations have met with little or no success. Topical fluoride applications to the teeth as well as dietary supplements of fluoride have been successful in strengthening the hydroxyapatite crystal lattice structure of enamel with a concomitant decrease in the rate of tooth decay.
Methods of disease control directed to the microbial flora in the mouth is the latest area to receive consideration. Since the role of microorganisms in the disease process is now known, attempts at control through the use of chemotherapeutic agents is desirable. Antibiotics such as penicillin, erythromycin, vancomycin and spiramycin have been shown to control the dental disease process either through a cidal effect on the causative organism or through a plaque-inhibiting process. However, the widespread use of these antibiotics could lead to resistant strains of microorganisms, potentially rendering the antibiotics useless in life-threatening situations. Because of this, it is felt that the widespread use of antibiotics in dental prophylaxis is not feasible.
Consequently, it would be desirable to utilize an anti-microbial which has a sufficiently broad spectrum to eliminate from the oral cavity organisms known to be cariogenic or that cause dental pathologies. Similarly, it would be desirable that this anti-microbial and compositions containing it be effective in low doses, and not cause staining of the teeth and oral mucosa, nor should it cause other oral irritation.